Classification and functions of enteroendocrine cells of the lower gastrointestinal tract.

With over thirty different hormones identified as being produced in the gastrointestinal (GI) tract, the gut has been described as 'the largest endocrine organ in the body' (Ann. Oncol., 12, 2003, S63). The classification of these hormones and the cells that produce them, the enteroendocrine cells (EECs), has provided the foundation for digestive physiology. Furthermore, alterations in the composition and function of EEC may influence digestive physiology and thereby associate with GI pathologies. Whilst there is a rapidly increasing body of data on the role and function of EEC in the upper GI tract, there is a less clear-cut understanding of the function of EEC in the lower GI. Nonetheless, their presence and diversity are indicative of a role. This review focuses on the EECs of the lower GI where new evidence also suggests a possible relationship with the development and progression of primary adenocarcinoma.

Prognostic value of multiple cytokine analysis in colorectal cancer: a systematic review.

The link between inflammation and outcome has been established in colorectal cancer through experimental evidence demonstrating an influential role of pro-inflammatory cytokines on tumour growth and progression. Furthermore, prognostic scores based on overall markers of systemic inflammation such as C-reactive protein and neutrophil count have been validated. Over recent years, an increasing number of inflammatory cytokines have been identified as prognostic predictors in colorectal cancer and the aim of this review was to evaluate the literature on the prognostic value of multiple cytokine measurement. The English language literature published since the year 2000 was searched using terms including, 'colorectal cancer', 'cytokines' and 'prognosis' through Medline, Embase and Scopus databases. Reports were screened by two independent reviewers and studies evaluating fewer than three cytokines were excluded. Quality assessments were performed in six domains before data extraction was undertaken in duplicate. Seven studies were found to evaluate multiple cytokines after 570 records were screened. The quality of these studies ranged from poor to moderate and were heterogeneous in terms of the patient population and the number and selection of cytokines tested. Four studies combined multiple cytokine levels into a single score and found them to be predictive of prognosis whereas the association between individual cytokines and outcome was not demonstrated consistently. The combination of multiple cytokine markers into a single prognostic score shows promise in colorectal cancer and further research is required to establish and validate such a score.

Neoadjuvant therapy in rectal cancer: how are we choosing?

BACKGROUND: Neoadjuvant therapy has revolutionized the management of rectal cancer; however, there is a need to examine the factors driving neoadjuvant treatment allocation. This study aimed to describe patterns of treatment allocation for patients with rectal cancer at our institution and identify predictors for receiving neoadjuvant therapy, and for choice of short- or long-course therapy. METHODS: A retrospective review of a prospectively maintained database of 122 patients undergoing surgical resection for rectal cancer with curative intent, between 1 November 2012 and 31 October 2017. Univariate and multivariate analyses were performed to identify factors that determined which patients received neoadjuvant therapy, and whether it was short or long course. RESULTS: Eighty-six patients (70%) received neoadjuvant therapy. Independent predictors for receiving neoadjuvant therapy were T3-4 tumours (P < 0.001), node-positive disease (P = 0.005) and mid (P = 0.045) or low rectal cancers (P < 0.001). Of those receiving neoadjuvant therapy, 38 (44%) received short course and 48 (56%) received long course. Node-positive disease was the only predictor for receiving long rather than short-course neoadjuvant therapy (P = 0.002). Overall, these factors predicted 76% of neoadjuvant treatment allocation. Our predictor model identified important areas of variance in our decision-making. CONCLUSION: Utilizing the identified factors, it appears that consistent decisions regarding neoadjuvant therapy are being made the majority of the time. These decisions are largely driven by T and N stage as well as tumour height. Mesorectal fascia involvement, pre-treatment carcinoembryonic antigen, age and comorbidity also influenced decision-making to a lesser and more variable extent.

Pre-operative carcinoembryonic antigen predicts survival following colorectal cancer surgery with curative intent.

BACKGROUND: Circulating biomarkers may be of value in providing additional prognostic information to the TNM staging system. Previous population-level studies suggest a prognostic role for pre-operative carcinoembryonic antigen (CEA). The purpose of this study is to verify the prognostic role of pre-operative CEA at the individual level, in a New Zealand cohort of colorectal cancer patients. METHODS: Retrospective cohort study of patients undergoing potentially curative surgery for colorectal adenocarcinoma between 2010 and 2012 at a tertiary hospital in New Zealand. One hundred and thirty-nine patients had pre-operative CEA data available and were included in the study. The main outcomes measured were overall survival (OS) and disease-free survival (DFS) over a minimum of 5 years of follow up. RESULTS: Pre-operative CEA was requested in 138 out of 237 (58.2%) patients undergoing surgery. The median age was 71 years and median follow-up duration 61 months. High CEA was not associated with the incidence of disease recurrence (P = 0.69). A significant difference was found between high and low CEA for OS (P = 0.09) and DFS (P = 0.04). On multi-variate survival analysis, pre-operative CEA was identified as an independent predictor of OS (HR 2.50, 95% CI 1.17-5.36, P = 0.02) and DFS (HR 1.78, 95% CI 1.02-3.13, P = 0.04). CONCLUSION: We identified pre-operative CEA as an independent predictor of OS and DFS on an individual level. CEA offers additional prognostic value to TNM staging and should be requested routinely as part of the pre-operative work-up.

Disease recurrence following surgery for colorectal cancer: five-year follow-up.

AIM: To describe the patterns of recurrence in a contemporaneous cohort of patients undergoing surgery with curative intent for colorectal adenocarcinoma at a New Zealand hospital with five-year follow-up. METHODS: Patients with colorectal cancer undergoing potentially curative surgery between January 2010 and December 2012 were followed up for a median of 61 months with three-monthly CEA (carcinoembryonic antigen), a colonoscopy after one year and yearly computed tomography scans of the chest, abdomen and pelvis for the first three years. RESULTS: Overall, 59/237 (24.9%) of patients experienced disease recurrence, the most common sites being the liver, followed by the lung and local recurrence. Recurrence rates did not differ significantly between colon and rectal cancer and ranged from 5.1% in stage I to 60% in stage IV. Seventy-three percent of all recurrences were observed within the first 24 months post-operatively. CONCLUSION: While New Zealand outcomes in colorectal cancer have historically compared unfavourably against international standards, the outcomes observed in this cohort are encouraging and may reflect advances in care, including multidisciplinary team discussion, increased use of adjuvant therapy, surgical subspecialisation and protocolled surveillance and follow-up.